title: DNA double strand breaks induced by the indirect effect of radiation are more efficiently repaired by non-homologous end joining compared to homologous recombination repair.
abstract: The aim of this study was to investigate the relative involvement of three major DNA repair pathways, i.e., non-homologous end joining (NHEJ), homologous recombination (HRR) and base excision (BER) in repair of DNA lesions of different complexity induced by low- or high-LET radiation with emphasis on the contribution of the indirect effect of radiation for these radiation qualities. A panel of DNA repair-deficient CHO cell lines was irradiated by (137)Cs γ-rays or radon progeny α-particles. Irradiation was also performed in the presence of 2M DMSO to reduce the indirect effect of radiation and the complexity of the DNA damage formed. Clonogenic survival and micronucleus assays were used to estimate efficiencies of the different repair pathways for DNA damages produced by direct and indirect effects. Removal of the indirect effect of low-LET radiation by DMSO increased clonogenic survival and decreased MN formation for all cell lines investigated. A direct contribution of the indirect effect of radiation to DNA base damage was suggested by the significant protection by DMSO seen for the BER deficient cell line. Lesions formed by the indirect effect are more readily repaired by the NHEJ pathway than by HRR after irradiation with γ-rays or α-particles as evaluated by cell survival and the yields of MN. The results obtained with BER- and NHEJ-deficient cells suggest that the indirect effect of radiation contributes significantly to the formation of repair substrates for these pathways.
authors.affiliation: Centre for Radiation Protection Research, Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, SE-106 91 Stockholm, Sweden; Faculty of Medicine, University of Latvia, LV-1586 Riga, Latvia. Electronic address: ainars.bajinskis@su.se.
authors.forename: Ainars
authors.initials: A
authors.lastname: Bajinskis
authors.forename: Adayapalam T
authors.initials: AT
authors.lastname: Natarajan
authors.forename: Klaus
authors.initials: K
authors.lastname: Erixon
authors.forename: Mats
authors.initials: M
authors.lastname: Harms-Ringdahl
mesh_terms: D000818:Animals; D016466:CHO Cells; D002470:Cell Survival; D002588:Cesium Radioisotopes; D002645:Chickens; D003114:Colony-Forming Units Assay; D006224:Cricetinae; D003412:Cricetulus; D053903:DNA Breaks, Double-Stranded / Q000528:radiation effects*; D059766:DNA End-Joining Repair / Q000235:genetics*; D049914:DNA Repair-Deficiency Disorders / Q000235:genetics*; D005720:Gamma Rays / Q000009:adverse effects*; D015162:Micronucleus Tests; D017687:Radon Daughters / Q000009:adverse effects*; D059767:Recombinational DNA Repair / Q000235:genetics*
chemical_list: D002588:Cesium Radioisotopes; D017687:Radon Daughters
keywords: High-LET radiation; Homologous recombination; Indirect effect; Non-homologous end joining